Ultrasound-actuated platelet mimetic nanomotors enable targeted piezocatalytic ROS storm for precision thrombolysis

Thrombotic diseases pose life-threatening risks, yet current thrombolytic therapies face limitations including poor targeting and bleeding risks. To address this, ultrasound-activatable nanomotors (hBT-Pt@Pm) were developed through the integration of hollow BaTiO₃/Pt Schottky heterojunctions with platelet membrane (Pm) coatings. The hollow structure enhances piezocatalytic efficiency by shortening charge migration distances, while Pt deposition improves carrier separation, collectively boosting reactive oxygen species (ROS) generation under ultrasound. Finite element simulations confirmed a 5.8-fold increase in piezoelectric potential compared to solid BaTiO₃. Asymmetric Pt caps enable cavitation-driven thrombus penetration, and Pt-mediated H₂O₂ decomposition generates O₂ bubbles to amplify ROS production. In vitro, Pm coating conferred 5.2-fold higher thrombus accumulation than non-targeted nanoparticles. In murine venous thrombosis models, the nanomotors achieved near-complete clot dissolution via synergistic piezocatalysis and mechanical penetration, without systemic toxicity. This approach provides a targeted, ultrasound-powered alternative to conventional thrombolytics, combining precision therapy with inherent biosafety.